Evaluation of the Symptom-Based Diagnostic Criteria for Irritable Bowel Syndrome in Conjunction With Clinical Examinations and Laboratory Investigations

Background Irritable bowel syndrome (IBS) is a chronic condition characterized by persistent abdominal pain or discomfort and impaired bowel function. Symptoms often vary in onset and severity, are worse during flare-ups, and affect the patient's quality of life. A positive diagnosis of IBS based on clinical symptoms may lead to a better outcome. There are different diagnostic criteria like Kruis score, Manning criteria, Rome I, II, III, and IV criteria, and each new one addresses the deficiencies of the previous ones. We analyze the effectiveness of the most commonly used diagnostic criteria associated with clinical examinations and laboratory tests in treating IBS in these studies. Methodology This is a retrospective study in which data from IBS subjects were collected by simple random sampling and compared using Manning criteria, Kruis score, and Rome IV criteria. Laboratory tests included complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Of the 130 patients, IBS is more prevalent in adults aged 30-50 years, with a male predominance. The Kruis score outperformed the Manning criterion in distinguishing between organic bowel disease and IBS. This, together with the Rome IV criteria, increases the likelihood of identifying IBS. Conclusions Differentiating IBS from functional and organic gastrointestinal problems is critical. Irritable bowel syndrome can be diagnosed using symptom-based diagnostic criteria. Clinical observation and physical examination should be supplemented with laboratory indicators.


Introduction
Irritable bowel syndrome (IBS) is difficult to diagnose due to several factors [1,2]. Studies have found that four symptoms are the most common in IBS sufferers -bloating, pain relief with bowel movements, and loose and frequent bowel movements with the onset of pain [3,4]. A careful analysis can increase the diagnostic reliability (to positively diagnose IBS with 99% accuracy, the minimum score was 44 points) and reduce the examination effort for IBS. Kruis et al. found that a detailed history, physical examination, and basic laboratory tests are sufficient for a positive diagnosis of IBS [5]. Talley et al. concluded that the Manning criteria distinguish irritable bowel syndrome from organic gastrointestinal disease [6,7]. Soft and watery stool often served as an independent criterion. Jeong et al. and Boyce et al. concluded that the prevalence of IBS according to Manning, Rome I, and Rome II was 13.6%, 4.4%, and 6.9%, respectively [8,9,4]. Doğan and Unal showed that when the Manning criteria and the Kruis scoring system were applied together, these systems showed a strong correlation in IBS but not in esophagogastroduodenoscopy (OGD) [8,9]. Jellema et al. found that symptom-based IBS criteria cannot rule out organic disease and recommended that the Rome III criteria be reviewed in primary care [9,10]. This study evaluated the usefulness of the Manning, Kruis, and Rome IV criteria for IBS diagnosis using various standard definitions and attempted to determine the degree of agreement between these definitions. Repeated examinations should be avoided and the Bristol stool chart should be used to objectively describe bowel patterns and assign patients to the appropriate subtype [11].

Study design and setting
This retrospective observational cohort study was conducted from September 2019 to February 2020 on 130 IBS patients in the outpatient department of the Department of Surgery at the Vydehi Institute of Medical Sciences and Research Centre, Bangalore. In the first appointment, a thorough medical history was taken and a physical examination was performed on each patient. Prior to their diagnostic assessment, all patients who consented to participate completed the questionnaire. The questionnaire and scoring method for IBS was based on Manning criteria [6,7] and Kruis score [5]. The Rome IV criteria served as a comparison [2]. Investigations included complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum albumin. Statistical software SPSS 22.0 (Armonk, NY: IBM Corp.) and R environment version 3.2.2 (Indianapolis, IN: The R Foundation) were used for the analysis of the data. Additionally, Microsoft Word and Excel were used to create graphs, tables, etc.

Inclusion and exclusion criteria
Inclusion criteria included consenting patients over the age of 18 years who have had abdominal pain, bloating, and irregular bowel movements for more than six months. Exclusion criteria included patients with a history of organic gastrointestinal disease, patients on ventilator support due to acute respiratory distress syndrome (ARDS), patients with recurrent gastrointestinal infections, colorectal cancer, microscopic, lymphocytic, and collagenous colitis, celiac disease, inflammatory bowel disease (IBD), primary bile acid diarrhea, immune deficiency, and uncontrolled thyroid disease. Individuals with a history of liver disease or those whose liver enzyme levels were above normal were not included in the study. In addition, people who have undergone abdominal radiation or surgery other than appendectomy or cholecystectomy were excluded.

Statistical methods
This study performed a descriptive and inferential statistical analysis of Rome IV and compared it with Kruis and Manning tests. Results of continuous measurements are presented as mean standard deviation (minmax), and results of categorical measurements are presented in counts (%). Significance is assessed at a 5% level of significance. Assumptions were made about the data, e.g., that dependent variables should be normally distributed, samples drawn from the population should be random, and the cases of the samples should be independent. Student's t-test (two-tailed, independent) was used to find the significance of the study parameters on a continuous scale between two groups (intergroup analysis). Levene's test of homogeneity of variance was used to assess homogeneity. Chi-square/Fisher's exact test was used to determine the significance of study parameters on a categorical scale between two or more groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy levels were calculated to determine the diagnostic properties of Rome IV when compared to Kruis and Manning criteria. P-value=0.05<p<0.10 was considered suggestively significant, p-value 0.01<p≤0.05 was considered moderately significant, and p-value≤0.01 was considered strongly significant.

Results
According to Table 1, the majority of patients (n=40, 30.8%) belonged to the age group of 41-50 years. This is followed by the second largest group of people (n=36, 27.7%) in the age group between 30 and 40 years. IBS is believed to be more common in people between the ages of 30 and 50 years, who make up more than 50% of the study participants.

Discussion
IBS is a persistent and debilitating disease that affects between 9% and 23% of the world's population, with 12% seeking medical treatment in primary care [1]. Anand et al. found that 33% of IBS symptoms are caused in middle-aged men, with the prevalence increasing with age [11,12]. About a third of the patients see a doctor [11]. In our study, more than 22.3% of participants had an elevated ESR. CRP was elevated in 34.6%; 13.1% of participants had low hemoglobin levels, and it was observed that WBC increased by 6.2%. We found no anemia in the participants with IBS. Ford et al. found that single symptoms have limited accuracy in diagnosing IBS, and the Manning and Kruis scoring systems are only moderately accurate [12]. Despite widespread acceptance, only the Rome I categorization has been validated [13].
Whitehead and Drossman reviewed the evidence for the validity of symptom-based criteria for irritable bowel syndrome (Manning, Rome I, Rome II, and Rome III) [13,14]. Two types of validations have been reported -first, studies examining whether symptom criteria distinguish patients with structural disease from those without structural disease at colonoscopy, and second, whether symptom criteria distinguish individuals with IBS by positive diagnosis from healthy subjects or patients with other functional and structural disorders. Both types of research confirm the validity of the symptom-based IBS criteria. Rome III investigations are required. IBS has a significant impact on rural populations, with CRP levels being higher in IBS patients than in healthy controls [12]. However, they remain within normal laboratory values [15]. According to Halpin and Ford, symptoms consistent with IBS were significantly more common in patients with IBD than controls without IBD, even in those presumed to be in remission [16]. IBS-like symptoms were also much more common in Crohn's disease (CD) patients than in ulcerative colitis (UC) patients. Treatment options for IBD patients with IBS symptoms are critical.
Hauser et al. reported in a prospective study that IBS patients with higher ESR had a lower health-related quality of life (HRQoL), but there is no association between ESR and disease severity or overall HRQoL [17]. Lovell and Ford found in a meta-analysis that the prevalence of IBS varies across countries, with women being affected more often than men, but socioeconomic status has not been adequately studied [18]. Ford et al. found that more reliable IBS diagnostic approaches are needed to distinguish between IBS and organic diseases [19]. A systematic review and meta-analysis by Menees et al. to determine the efficacy of CRP, ESR, fecal calprotectin, and fecal lactoferrin in inflammatory bowel disease in patients with irritable bowel syndrome showed that CRP and calprotectin levels of 0.5 and 40 rule out IBD in IBS symptoms and improve diagnosis [20]. Oka et al. found that global IBS incidence varied significantly even when using the same diagnostic criteria and techniques. Rome IV criteria may be less relevant than Rome III criteria for population-based epidemiological surveys [21].

Limitations
First, the IBS patients from the included studies were defined using various criteria such as Manning criteria and Rome IV. Additionally, the IBS patients from the included studies are uncertain about the active phase or remission phase. Second, since the questionnaire represents the definition of IBS, the average score may be biased. Third, more studies are needed to determine if changing these criteria may improve accuracy. Fourth, a smaller sample yields a result that may not be sufficiently meaningful to detect a difference between groups, and the study may turn out to be a false negative indicating that a person does not have a specific disease.

Conclusions
Existing diagnostic criteria do not distinguish IBS from organic disease, so a more detailed history and physical examination are needed to diagnose it. Laboratory markers should be used as a supplement to clinical observation and physical examination. In conclusion, our findings suggest that irritable bowel syndrome can be diagnosed using this scoring system, thereby addressing its numerous challenges. Further studies are needed to determine if changing these criteria can result in improved accuracy. We suggest that validation of the Rome IV criteria for population-based epidemiological surveys may be required. Currently used biomarkers are CRP, ESR, perinuclear antineutrophil cytoplasmic antibodies (pANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and fecal calprotectin; other biomarkers are yet to be confirmed in large clinical trials.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Vydehi Institute of Medical Sciences and Research Centre, Bangalore issued approval N/A. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.